Balance of Th1 and Th17 effector and peripheral regulatory T cells

Abstract

Transfer of antigen-specific T cells into antigen-expressing lymphopenic recipients leads to the sequential generation of Th1 and Th17 effector and protective CD25(+)FoxP3(+) regulatory cells in the periphery with surprisingly different kinetics. Such an experimental model is potentially valuable for defining the stimuli that regulate lineage decision and plasticity of various T cell effectors and peripheral regulatory T cells. Our studies have shown that IL-17 production occurs rapidly and declines within the first week with the appearance of IFN-gamma producing T cells. Regulatory T cells appear during the recovery phase of the disease. The factors that mediate this complex differentiation originating from a starting naïve T cell population remain to be defined.

Figure 1. DO11 IL-17 KO T cells cause less alopecia

1 × 10⁶ sorted CD4⁺CD25⁻ DO11 T cells from either WT or IL-17 KO mice were transferred into sOVA Tg Rag−/− recipients and alopecia was scored over time (alopecia < 1 cm = 1, 1 – 2 cm = 2, and > 2 cm = 3 points, respectively).

Figure 2. Model of plasticity and lineage relationship of Th1, Th17 effector cells and regulatory T cells

Transfer of naïve CD4 T cells into lymphopenic antigen-expressing recipients leads to initial Th17 development that is followed by predominance of IFN-γ producing cells. Peripherally generated regulatory T cells appear during the recovery phase of the disease.